In the medical field, in particular in surgery, it may be of great clinical utility being able to modulate the activation of tissue repair and the regeneration processes which are at the basis of the healing processes. In this context some surgical articles of manufacture, such as, for example, sutures, membranes, osteosynthesis plaques, made of re-absorbable materials able to favour the completion of the various reparatory phases and which do not need further surgical intervention for their removal, are extremely useful. It is an advantage to load these products of manufacture with pharmacologically active substances. In fact, the possibility of local diffusion of a drug through biocompatible and re-absorbable matrixes offers the advantage of a drastic reduction of the systemically administered dose and, as a consequence, of related side-effects. A limit of these systems is the reduced capacity of ensuring an adequate local release of the drug.
There are known release systems constituted by active substances added to a polymer matrix (U.S. Pat. No. 5,466,462) or polymer matrixes possibly containing inorganic products (WO 2004/098574). The limit of these systems is the extreme velocity with which the active substance is released from the matrix and the difficulty in modulating this parameter.
In particular WO 2004/098574 foresees the addition to the matrix of powders of various either lamellar or non-lamellar inorganic solids, with the dimension of nanoparticles. The process of adding the inorganic material is not described as critical and, in the case of extrusion, foresees a simple mixing of the various components all together. Further, in the preparation example reported in WO 2004/098574 it is specified that the powders do not undergo any preliminary treatment and the three components (PEG polymers, inorganic Cloisite and the active substance, Paracetamol) are all mixed together. The resulting system is characterised by an almost total release of the active substance in an extremely short interval (60 minutes).
It is known that some lamellar solids are able to absorb and release active substances (AAPS Pharm. Sci. Tech. 2002; 3 (3) art. 26) but unfortunately as they appear in the form of microcrystalline or finely subdivided amorphous powders they do not have suitable characteristics for taking on well defined solid forms (membranes, plaques, screws, etc.). Also, the release times of the active substance are very short, in the order of 24 hours, or less (100 minutes, as reported in Int. J. of Pharmaceutics 220 (2001) 23-32).
The need was felt to have a release system able to release the active substance contained in it, with times longer than 24 hours, possibly also longer than 5 days, and, if possible, to have a release modulated over time.